The goal of our research is to learn how the decision is made whether an RNA molecule is retained in the cell nucleus or released to the cytoplasm. It seems likely that the pattern of complexation of proteins with the RNA plays an important role in this process. Our immediate objective is to determine the structure of nuclear ribonucleoprotein complexes (RNPs). Previous studies have been concerned primarily with RNPs that may be extracted from isolated nuclei and are found to consist of diverse, short-lived nuclear RNA molecules in association with six polypeptides. We propose to analyze the structure of RNPs in situ by nuclease digestion experiments on intact nuclei. We shall focus on a particular set of RNPs, containing precursors of globin mRNA, in Friend erythroleukemic cells. Preliminary work has revealed both a repeating structure of coding regions of globin mRNP in the Friend cell nucleus, and a distinct repeating structure of the poly(A) portion of the mRNP in the cytoplasm. Reconstitution of these repeating structures will serve as an assay for isolation of the proteins involved, and also as a means of forming RNPs from the purified proteins for structural analysis. The relationship of RNP structure to RNA processing and transport can be studied by virtue of two further findings from preliminary work. First, globin sequences in Friend cell nuclei are mostly in the form of precursor RNA before induction of globin synthesis and mRNA following induction; this is indicative of gene regulation at the level of RNA processing, and permits the comparison of RNP structure before and after processing. Second, the repeating structure of poly(A) is formed upon transport to the cytoplasm, and this coupling of structure formation to transport can be observed in an in vitro system.